Reentrant orbital order and the true ground state of LaSr2Mn2O7.

Contrary to conventional wisdom, our purified La 2-2x Sr 1+2x Mn2O7 crystals exhibit CE-type orbital and charge order as the low-temperature ground state for a hole doping level h=0.5. For small deviations from h=0.5, the high-temperature CE phase is replaced at low temperatures by an A-type antiferromagnet without coexistence. Larger deviations result in a lack of CE order at any temperature. Thus, small inhomogeneities in cation or oxygen composition could explain why others commonly see this reentrance with coexistence.

First-order metal-insulator transitions in manganites: are they universal?

Conductivity data for La(2-2x)Sr(1+2xMn2O7 (x = 0.6) show a first-order transition from an orbital- or charge-ordered insulator to a metal as the temperature falls below approximately 160 K. The change in conductivity is 100 times larger than that seen previously in any single-phase manganite in zero field. The metallic low-temperature state is similar to x = 0.58, but x = 0.58 shows no evidence of orbital or charge order. This result supports a conclusion that strongly coupled magnetic-conductive transitions are first order.

Spin incommensurability and two phase competition in cobaltites.

The perovskite LaCoO3 evolves from a nonmagnetic Mott insulator to a spin cluster ferromagnet (FM) with the substitution of Sr2+ for La3+ in La1-xSrxCoO3. The clusters increase in size and number with x and the charge percolation through the clusters leads to a metallic state. Using elastic neutron scattering on La1-xSrxCoO3 single crystals, we show that an incommensurate spin superstructure coexists with the FM spin clusters. The incommensurability increases continuously with x, with the intensity rising in the insulating phase and dropping in the metallic phase as it directly competes with the commensurate FM, itinerant clusters. The spin incommensurability arises from local order of Co3+-Co4+ clusters but no long-range static or dynamic spin stripes develop. The coexistence and competition of the two magnetic phases explain the residual resistivity at low temperatures in samples with metalliclike transport.

Cytotoxicity of paclitaxel in combination with cisplatin and a new Pt-mercaptopyridine complex.

In vitro synergy has been reported for exposure to paclitaxel prior to cis-platin (cis-DDP), whereas the reverse sequence resulted in antagonism. There is no clear evidence for an intracellular origin of the schedule-dependent interaction, but several hypotheses have been proposed, such as effects at the level of DNA crosslinks, or binding to tubulin sites. The purpose of this study was to evaluate the cytotoxicity of these two drugs as single agents, in combination and in sequence, against a human colon adenocarcinoma cell line (LoVo). Moreover, we considered the new Pt-mercaptopyridine complex C/2, was like cis-platin in being able to alter DNA conformation. We have therefore studied the cytotoxic effects after single agent exposure, concomitant exposure (paclitaxel + cis-platin and paclitaxel + C/2) and sequential drugs exposure (paclitaxel-->cis-platin and cis-platin-->paclitaxel or paclitaxel-->C/2 and C/2-->paclitaxel). Our results demonstrate that the most cytotoxic effect is induced by paclitaxel and C/2 exposure both in the case of concomitant cell treatment and sequential exposure paclitaxel-->C/2.

A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line.

This study was designed to compare the activity of two MDR modulators, verapamil and dipyridamole, on the in vitro growth of a human colon carcinoma cell line. The aims were: a) to investigate the different sensitivity of the parental cell line (LoVo S) and the doxorubicin-resistant one (LoVo R) towards the treatment with several antiblastics and their associations with verapamil or dipyridamole; b) to evaluate if the combined use of these drugs with verapamil or dipyridamole increases their cytotoxicity; c) to understand whether the mechanism of action of each modulator is the same. Idarubicin and vinblastine were the most active drugs on both cell lines. LoVo R cells showed cross-resistance to vinblastine, teniposide and mitoxantrone, while chemosensitivity towards cisplatin and cyclophosphamide was almost the same in both cell lines. The inhibitory effect on cell growth was enhanced when the drugs were associated with verapamil, but no difference was detected with cisplatin and cyclophosphamide. Verapamil is thus an effective MDR modulator when used with drugs actively pumped out of tumour cells by P-glycoprotein, while it is ineffective with drugs that induce resistance by different mechanisms. When combined with dipyridamole, a significant result was observed in the case of cisplatin, where a marked increase of cytotoxicity was detected.

In vitro effect of Pt and Pd mercaptopyridine complexes.

In previous research we studied the cytotoxic effect of new Pt mercaptopyridine (MP) complexes on several tumoral cell lines (F10, Föhn, LoVo and HeLa) as well as on the fibroblast cell line (3T3). The more interesting Pt compounds are compared here to Pd mercaptopyridine analogs, in order to evaluate the metals influence on activity. Earlier, the complexes C/2 = [Pt(MP)3Cl]Cl; C/5 = [Pt(MP)3Br]Br; C/8 = [Pd(MP)3Cl]Cl and C/11 = [Pd(MP)3Br]Br and cis-DDP as reference were tested on 3T3 and LoVo cells, by Sauter's multiwells technique and neutral red uptake. The results obtained using lysosomal neutral red uptake to confirm those by the Sauter's multiwells techniques, showing that C/2 and C/11 are the most active complexes. In particular, C/2 shows a significantly higher cytotoxic activity than cis-DDP on LoVo cells, and equivalent on 3T3. C/5 complex also induces an interesting cell growth reduction, but only on LoVo, while C/8 is completely inactive on all cell lines. Because the major limitation to the successful treatment of platinum-based chemotherapeutic regimens is the emergence of drug resistance, the activity of the four complexes on cis-DDP sensitive (M5076) and cis-DDP resistant cancer cells (M5/DDPc) has been tested. The data reported in this work make devident that the presence of ligands with sulfur donor atoms may be of particular importance in confirming the antitumor properties of Pt complexes. In fact, Pt mercaptopyridine C/2 is also more active than cis-DDP against cells made resistant to cis-DDP. Moreover, the results obtained with Pd complex C/11, especially on LoVo cells, showed that this metal could be considered interesting in the design of potential new antitumor drugs.

Use of decision analysis in a family practice residency for a patient with an abdominal aortic aneurysm.

BACKGROUND: A patient at the Tatem-Brown Family Practice Center with many medical problems asked for advice about elective surgical resection of a large abdominal aortic aneurysm. METHODS: The best course of action was not obvious, so a decision tree was constructed using data from the medical literature and the patient's rating of several quality of life issues. RESULTS: Elective surgery was the optimal choice for this patient, but the decision was sensitive to values chosen for two variables in the decision model. CONCLUSION: Decision analysis has benefits in a family practice residency. Residents become familiar with vigorous literature review and decision-analytic tools and principles. They gain a deeper knowledge of the patient, due to the need to understand the patient's relative values for potential outcomes of medical intervention.

Effect of dipyridamole, 5'-(N-ethyl)-carboxamidoadenosine and 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine on LOVO cell growth and morphology.

The effects of stable compounds acting on adenosine receptors, 5'-(N-ethyl)-carboxamidoadenosine (NECA: A2 and A1 adenosine receptor agonist) and 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX: selective A1 adenosine receptor antagonist) were evaluated in vitro on doxorubicin-resistant LoVo (LoVo-R) and doxorubicin-sensitive LoVo (LoVo-S) human metastatic cell lines by using the neutral red test for cell growth. The effect of dipyridamole, an adenosine uptake inhibitor, was also evaluated. The drugs had an inhibitory effect on LoVo cell growth. The association of the drugs with doxorubicin enhanced the inhibition of cell growth, particularly for NECA and PACPX on LoVo-R cells. Morphological observation with scanning electron microscopy indicated cytotoxicity of the tested compounds, alone or in association with doxorubicin both in LoVo-R or LoVo-S cells, supporting the hypothesis of inhibitory effect on tumor cell growth.

The effect of cis-DDP and Pt mercaptopyridine complexes on cell lines in vitro.

The effect of Platinum (II) complexes with mercaptopyridines on cell lines (fibroblasts 3T3 and the tumour ones F10, Föhn, Lovo) were studied. Synthesis and characterization of the compounds are reported together with the preliminary in vitro tests. Data obtained on cytopathogenic effect (CPE), cell growth and colony forming ability demonstrated that all the platinum mercaptopyridines tested are more active than cisplatin in the same conditions.

Increased spontaneous cell detachment of F10 cells induced in vitro by some calcium-channel blockers.

We investigated the action of some Ca(++)-channel blockers such as flunarizine, nifedipine and verapamil on F10 cells in vitro. Cell adhesion to the growth substratum, evaluated by the technique of spontaneous detachment in culture medium, is reduced in Ca(++)-channel blocker treated cells by comparison with controls. In our opinion such an event could also explain the inhibitory effect on cell growth and colony forming ability.

The effect of Dilazep on F10 cells in vitro.

Experiments on F10 cell growth, colony ability, cell adhesion and ultramorphology at SEM have been performed. The effect of Dilazep (DIL) has been compared with that of well known modulating agents such as Flunarizine (FLU) and Verapamil (VER) on cells cultured in high Ca++ medium (HCM) and in low calcium medium (LCM). While in HCM there is no difference among the three drugs, FLU and VER had a stronger effect on cell growth inhibition in LCM. Cell adhesion to the growth substratum, evaluated by the technique of spontaneous detachment in culture medium, is reduced in DIL treated cells in comparison to the controls.

The mid-trimester placenta previa: a prospective follow-up.

One hundred and fifty-six mid-trimester sonograms were performed at our prenatal diagnostic unit. Twenty women were found to have a low-lying placenta or placenta previa and were followed by serial ultrasound examinations to observe changes in placental position. Eighty percent of women, i.e., 16/20, with a low-lying placenta had converted to normal implantation by the time of delivery. Most of the conversions had taken place at approx. 34 weeks of gestation. The patients with mid-trimester low-lying placenta had an increased risk of third-trimester bleeding, abruptio placentae and cesarean sections. The infants were also at risk of premature delivery. Patients with mid-trimester low-lying or placenta previa should be followed by ultrasound to monitor delivery.

Arginine 2-mercaptoethane sulfonate and sodium 2-mercaptoethane sulfonate: a comparative study of their effects upon tumour cells.

The action of arginine 2-mercaptoethane sulfonate in comparison with sodium 2-mercaptoethane sulfonate on cell growth and cell adhesion of a metastatic sub-line of murine melanoma (F10/B16) was investigated. The capability of the two compounds to interfere with the cytotoxicity of 4-hydroperoxycyclophosphamide and of cis-dichlorodiammineplatinum(II) in F10 cells was studied. The in vivo studies included the determination of acute and sub-acute toxicity of the two salts on mice. Very low toxicity and no significant differences between the two compounds were detected.

Effects of 6,6'-dithiodinicotinic acid (CPDS) and its metabolite 6-mercaptonicotinic acid (6-MNA) on murine and hamster fibroblasts (3T3 and BHK) and murine metastatic melanoma cells (F10).

We investigated the action of 6,6'-dithiodinicotinic acid (CPDS) and its metabolite 6-mercaptonicotinic acid (6-MNA) in vitro on murine (3T3) and baby hamster kidney (BHK) fibroblasts and an in vivo highly metastatic subline of murine B16 melanoma (F10). CPDS determined an inhibition of cell growth and a decrease in cell adhesion, while 6-MNA had no effect. When combined with data of the mitotic index and endogenous purine ribonucleotides (on which the drugs seem to have no effect), these observations are conceivable with the hypothesis that the primary target of CPDS is cell membrane.

Effect of peptichemio and of peptichemio plus hydrocortisone on growth and alkaline phosphatase activity in HeLa cells in vitro.

The actions of Hydrocortisone, Peptichemio and of Peptichmio + Hydrocortisone mixture in HeLa cells have been experimented. The results show an increase of cell number in the controls and a lower, but not statistically different growth, in the Hydrocortisone-treated cultures. In the cultures treated with peptichemio the growth is hardly evident, in the ones treated with the Hydrocortisone + Peptichemio mixture, the cell number is decreasing with time. ALP activity in cells treated with drugs is much higher than in the controls ones. The results either on cellular growth and on ALP activity, are compared to the Ara C ones. No significant difference in media ALP activity between drug-treated cultures and controls is evidentiated. The results show in the Peptichemio + Hydrocortisone mixture, that the action of Hydrocortisone is overcome by the Peptichemio one. By the cytochemical technique the enzyme localization is particularly evident in the cytoplasmic inclusions, which are very numerous in the cells treated with Peptichemio.

Biochemical and cytochemical effects of cytosine arabinoside (ARA C) and hydrocortisone on HeLa cells.

The biochemical and cytochemical effects of cytosine arabinoside (Ara C) and of hydrocortisone on HeLa cell in vitro have been studied. In cultures treated with Ara C, a relationship exists between the cytocidal effects of the drug and an increase in alkaline phosphatase. Although hydrocortisone had no influence on the proliferative rhythm, it induced an increase in alkaline phosphatase. Results obtained with the cytochemical technique were evaluated, particularly in relation to enzyme localization.

Effect of some antiblastic drugs on HeLa cells.

The antiblastic effects of the antimetabolites MTS, Ara-C, Bleomycin of the alkylating Thiotepa, of Peptichemio (alkylating and antimetabolic) and of Peptichemio-Bleomycin combination, were compared after 24 and 48 hr of treatment on HeLa cells. Ara-C, which inhibits typical mitoses, Peptichemio and MTX, which inhibit atypical mitoses, Thiotepa, which induces the highest percentage of pyknotic nuclei, showed a considerable effect on the nucleus. Peptichemio, and the combination Peptichemio-Bleomycin showed a significant effect on the cytoplasm (induction of vacuoles). After MTX and Peptichemio treatments, and after Peptichemio-Bleomycin combination (1 mug/ml), eosinophilic inclusions were evident both after 24 and 48 hr.